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To this end, we synthesized a number of permethylated quinolinium analogues[17] guided by in silico calculation of partition coefficient (clogP).[26] Addition of hydrophobic methyl group substitutions around the quinolinium scaffold (previously shown to negatively impact NNMT inhibitory activity)[17] only slightly improved membrane permeability via passive transport as indicated by the low, but non-zero, permeability values for 1,8-diMQ and 1,2,4,8-tetraMQ (Table 1)

Data availability All data supporting the findings of this study, including processed results and figure source data, are provided in the Supplementary Information files

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43 On the other hand, another review of 26 studies in osteoarthritic dogs found undenatured type II collagen supplementation, at a typical dose of 10 mg per day for one to five months, increased mobility and physical activity, and reduced lameness